Methotrexate
(MTX) is one of the first-line treatments for moderate
to severe psoriasis, while the side effects caused by injection and
oral administration of MTX greatly restrict its clinical application.
Transdermal drug delivery offers a desirable alternative to the conventional
approaches, but the performances of the currently available skin penetration
enhancement techniques are not so satisfactory. To address these limitations,
we developed a dissolving microneedle (MN) patch made of hyaluronic
acid (HA) with excellent water solubility, biocompatibility, biodegradability,
and mechanical properties. The amount of MTX encapsulated in the needles
of the patch could be controlled during the fabrication process for
precise dosage. Interestingly, the MTX-loaded MNs successfully penetrated
imiquimod (IMQ)-induced thickened epidermis in mice and delivered
the drug intralesionally. Meanwhile, fast dissolution of HA endowed
the MNs with operability for patients. We found that the MTX-loaded
MNs not only showed well-maintained inhibitory effect in vitro but
also alleviated the psoriasis-like skin inflammation in mice. Moreover,
the MTX-loaded MNs were significantly more efficacious than taking
the same dose of drug orally. Consequently, a higher oral dose of
MTX was required for a comparable amelioration, which in turn increased
its systemic toxicity. Taken together, the proposed MTX-loaded dissolving
MN patch strategy provides a new opportunity for efficient and safe
treatment of psoriasis.
For superficial skin tumors (SST) with high incidence, surgery and systemic therapy are relatively invasive and possible to cause severe side effect, respectively. Yet, topical therapy is confronted with the limited transdermal capacity because of the stratum corneum barrier layer of skin. Therefore, it is crucial to develop a highly effective and minimally invasive alternative transdermal approach for treating SST. Here, we developed gold nanocage (AuNC)- and chemotherapeutic drug doxorubicin (DOX)-loaded hyaluronic acid dissolving microneedle (MN) arrays. The loaded AuNCs are not only reinforcers to enhance the mechanical strength of the MNs, but also effective agents for photothermal therapy to obtain effective transdermal therapy for SST. The resultant MNs can effectively penetrate the skin, dissolve in the skin and release cargoes within the tumor site. Photothermal effect of AuNCs initiated by near-infrared laser irradiation combined with the chemotherapy effect of DOX destroyed tumors synergistically. Moreover, we verified the potent antitumor effects of the DOX/AuNC-loaded MNs after four administrations to SST-bearing mice without obvious side effects. Therefore, the drug/AuNC-loaded dissolving MN system provides a promising platform for effective, safe, minimally invasive combined treatment of SST.
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